Case Control Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. May 15, 2025; 16(5): 103602
Published online May 15, 2025. doi: 10.4239/wjd.v16.i5.103602
Single-nucleotide polymorphisms in genes involved in folate metabolism or selected other metabolites and risk for gestational diabetes mellitus
Ting-Ting Zheng, Jia-He Liu, Wan-Tong Huang, Bo Hong, Di Wang, Chun-Yi Liu, Jie Zhang, Si-Si Li, Shao-Wei Wu, Qi Wang, Lei Chen, Lei Jin
Ting-Ting Zheng, Lei Chen, Department of Obstetrics and Gynecology, The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Ting-Ting Zheng, Department of Gynecology, Jinan Maternal and Child Care Hospital, Jinan 250000, Shandong Province, China
Ting-Ting Zheng, Lei Chen, Department of Obstetrics and Gynecology, The Sixth Medical Center of PLA General Hospital, Beijing 100191, China
Jia-He Liu, Wan-Tong Huang, Di Wang, Chun-Yi Liu, Jie Zhang, Si-Si Li, Lei Jin, Institute of Reproductive and Child Health, Peking University, Beijing 100191, China
Jia-He Liu, Wan-Tong Huang, Di Wang, Chun-Yi Liu, Jie Zhang, Si-Si Li, Lei Jin, Key Laboratory of Reproductive Health, National Health Commission of the People’s Republic of China, Beijing 100191, China
Jia-He Liu, Wan-Tong Huang, Di Wang, Chun-Yi Liu, Jie Zhang, Si-Si Li, Lei Jin, State Key Laboratory of Female Fertility Promotion, Peking University, Beijing 100191, China
Jia-He Liu, Wan-Tong Huang, Di Wang, Chun-Yi Liu, Jie Zhang, Si-Si Li, Lei Jin, Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
Bo Hong, Department of Obstetrics and Gynecology, Haidian Maternal and Child Health Care Hospital of Beijing, Beijing 100191, China
Shao-Wei Wu, Department of Occupational and Environmental Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an Jiaotong University Health Science Center, Xi'an 710000, Shaanxi Province, China
Qi Wang, Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China
Co-first authors: Ting-Ting Zheng and Jia-He Liu.
Co-corresponding authors: Lei Chen and Lei Jin.
Author contributions: Zheng TT and Liu JH contribute equally to this study as co-first authors; Chen L and Jin L contribute equally to this study as co-corresponding authors; Zheng TT was responsible for conceptualization, data curation, formal analysis, validation, visualization, writing-original draft, writing–reviewing and editing; Liu JH was responsible for conceptualization, data curation, formal analysis, investigation, project administration, software, validation, visualization, writing-original draft; Huang WT was responsible for data curation, formal analysis, investigation, project administration, software, writing-original draft; Hong B was responsible for formal analysis, investigation, project administration, writing-original draft; Wang D was responsible for investigation, project administration, software; Liu CY was responsible for data curation, investigation, project administration, software; Zhang J was responsible for data curation, investigation, project administration, software; Li SS was responsible for data curation, investigation, project administration, software; Wu SW was responsible for methodology, investigation, project administration, software; Wang Q was responsible for investigation, project administration; Chen L was responsible for conceptualization, funding acquisition, project administration, resources, supervision, writing–review and editing; Jin L was responsible for data curation, investigation, investigation, conceptualization, funding acquisition, project administration, resources, supervision, writing–review and editing.
Supported by the National Key Research and Development Program of China, No. 2021YFC2700700 and No. 2021YFC2700704; and Capital’s Funds for Health Improvement and Research (CFH) in People’s Republic of China, No. 2020-1-5112.
Institutional review board statement: The study was approved by the Biomedical Ethics Committee of Peking University (No. IRB00001052-18104).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at jinlei@bjmu.edu.cn.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Lei Jin, PhD, Professor, Institute of Reproductive and Child Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China. jinlei@bjmu.edu.cn
Received: December 9, 2024
Revised: February 9, 2025
Accepted: March 24, 2025
Published online: May 15, 2025
Processing time: 140 Days and 3.8 Hours
Abstract
BACKGROUND

There are conflicting results on the potential correlation between folic acid and gestational diabetes mellitus (GDM), and the correlation between genetic factors related to folic acid metabolism pathways and GDM remains to be revealed.

AIM

To examine the association between single-nucleotide polymorphisms (SNPs) of enzyme genes in the folate metabolite pathway as well as that between GDM-related genes and risk for GDM.

METHODS

A nested case-control study was conducted with GDM cases (n = 412) and healthy controls (n = 412). DNA was extracted blood samples and SNPs were genotyped using Agena Bioscience’s MassARRAY gene mass spectrometry system. The associations between different SNPs of genes and the risk for GDM were estimated using logistic regression models. The generalized multi-factor dimensionality reduction (GMDR) method was used to analyze gene-gene and gene-environment interactions using the GMDR 0.9 software.

RESULTS

The variation allele frequency of melatonin receptor 1B (MTNR1B) rs10830963 was higher in the GDM group than in controls (P < 0.05). MTNR1B rs10830963 mutant G was associated with risk for GDM [adjusted odds ratio (aOR): 1.43; 95% confidence interval (95%CI): 1.13-1.80] in the additive model. MTNR1B rs10830963 GG + GC was significantly associated with the risk for GDM (aOR: 1.65; 95%CI: 1.23-2.22) in the dominant model. The two-locus model of MTNR1B rs10830963 and CHEMERIN rs4721 was the best model (P < 0.05) for gene-gene interactions in the GMDR results. The high-risk rs10830963 × rs4721 type of interaction was a risk factor for GDM (aOR: 2.09; 95%CI: 1.49-2.93).

CONCLUSION

This study does not find an association between SNPs of folate metabolic enzymes and risk for GDM. The G mutant allele of MTNR1B rs10830963 is identified as a risk factor for GDM in the additive model, and there may be gene-gene interactions between MTNR1B rs10830963 and CHEMERIN rs4721. It is conducive to studying the causes of GDM and provides a new perspective for the precise prevention of this disease.

Keywords: Gestational diabetes mellitus; Folate; Gene; Deoxyribonucleic acid; Single nucleotide polymorphisms

Core Tip: Single-nucleotide polymorphisms of folate metabolic enzymes are not correlated with gestational diabetes mellitus (GDM). The G mutant allele of melatonin receptor 1B (MTNR1B) rs10830963 is a risk factor for GDM. Interactions between the MTNR1B rs10830963 and CHEMERIN rs4721 gene variants are associated with an increased risk for GDM.